Masayuki Fukase

Carcinosarcomas (malignant mullerian mixed tumors) of the uterus and ovary: a genetic study with special reference to histogenesis.

The histogenesis of carcinosarcomas (malignant mullerian mixed tumors) of the female genital tract is still not completely understood. In the present study, several different molecular pathologic techniques were applied to determine the histogenesis of 15 uterine and ovarian carcinosarcomas. The patterns of X-chromosome inactivation and the presence of p53 and K-ras mutations were analyzed in the carcinomatous and sarcomatous components. Microsatellite analysis was also performed. Ten tumors were monoclonal, one was biclonal (collision tumor), and another was probably biclonal; the other three were of indeterminate histogenesis. These data indicate that most uterine and ovarian carcinosarcomas are monoclonal.

ALPHA -FETOPROTEIN PRODUCING GASTRIC CARCINOMAS : A COMPARATIVE STUDY OF THREE DIFFERENT SUBTYPES

Nine cases of gastric carcinoma with excessive production of α‐fetoprotein (AFP) were analyzed morphologically, histochemically and biochemically. Consequently, it was proposed that AFP‐producing gastric carcinomas should be divided into three subtypes: (i) hepatoid type; (ii) yolk sac tumor‐like type; and (iii) fetal gastrointestinal type. The data from the study suggested that the hepatoid type and the yolk sac tumor‐like type are derived from liver cell metaplasia and yolk sac cell metaplasia of common poorly differentiated medullary adenocarcinoma, respectively. The fetal gastrointestinal type seemed to be a result of the imitation of fetal gastrointestinal epithelium by common tubular adenocarcinoma. The hepatoid type was also the most common in the file of AFP‐producing gastric carcinoma. Unfortunately, most of the hepatoid types seemed to be highly malignant.

Hypermethylation of the RUNX3 Gene Promoter in Testicular Yolk Sac Tumor of Infants

Testicular yolk sac tumor (YST) of infants is biologically distinct from its adult counterpart. Cytogenetically, YSTs in infants generally lack i(12p), which is highly characteristic of adult germ cell tumors (GCTs), whereas they frequently show a deletion of 1p36, indicating that the loss of a certain gene(s) in this region is an important event in the pathogenesis of infantile YSTs. In the present study, we examined 10 testicular YSTs from infants for promoter methylation status of the RUNX3 gene, localizing in 1p36.1, and loss of heterozygosity (LOH) in this region, on the presumption that RUNX3 acts as a tumor suppressor. Methylation of RUNX3 and LOH at 1p36.1 were detected in 8 of 10 (80%) and 6 of 8 (75%) infantile YSTs examined, respectively. All six cases harboring LOH showed RUNX3 methylation. In contrast, 0 of 12 adult GCTs showed RUNX3 methylation, and LOH at 1p36.1 was less frequent (1 of 6 cases: 16%) in adult GCTs. There is a significant difference in RUNX3 methylation between these 2 groups (P < 0.001). In normal testes of the young group, RUNX3 methylation was not detected. These results strongly suggest that RUNX3 is one of the tumor suppressors involved in the pathogenesis of testicular YSTs in infants.

Mucin expression in nonneoplastic and neoplastic glandular epithelia of the uterine cervix.

Although it is well known that the uterine cervix contains mucin-producing glandular epithelium, only a few studies have described the changes in mucin that accompany malignant transformation. In this study the authors evaluated the characteristics of mucin expression in the normal endocervical epithelium and mucinous and endometrioid adenocarcinomas of the uterine cervix. The normal endocervical epithelium was characterized by predominant sulfomucin and MUC1 expression in all sites and MUC5AC expression in the surface epithelium, while MUC2 was not detected at all and pyloric gland type mucin (using antibody HIK1083) was detected in less than 1% of cases. Cervical adenocarcinomas, especially mucinous adenocarcinomas, showed marked variability in mucin expression that included mucins of pyloric gland and intestinal type.

Alternate mucoid and hyalinized stroma in clear cell carcinoma of the ovary: manifestation of serial stromal remodeling

The stroma in ovarian clear cell carcinoma often shows alternate mucoid and hyalinized change. The hyalinized stroma is recognized to be an aberrant deposition of basement membrane material produced by tumor cells. The mucoid stroma, however, has drawn far less attention, and its significance remains unclear. We examined 60 ovarian clear cell carcinomas for the distribution and nature of the mucoid stroma. For comparison, 125 other surface epithelial ovarian tumors were examined. Twenty-nine of 60 (48%) clear cell carcinomas showed a mucoid stroma, either focally (21 cases) or diffusely (8 cases). The mucoid stroma in clear cell carcinomas was distinct from that in other surface epithelial tumors as follows: it showed a compact spherule-like appearance, commonly occupying the cores of small papillae. It also exhibited a cribriform pattern, resembling that of adenoid cystic carcinoma. It was rarely associated with stromal cells, despite the presence of abundant glycosaminoglycan including hyaluronan. Alternatively, it was strongly associated with hyalinized stroma. Among 40 clear cell carcinomas that had at least one type of stroma, 26 (65%) had both, either concomitantly or separately. The mucoid stroma tended to attenuate if the hyalinized stroma developed. In vitro, a clear cell carcinoma cell line, HAC-2, formed a spherule-like structure containing hyaluronan in the center, and a significant amount of hyaluronan was detected by latex agglutination immunoturbidimetry, indicating that HAC-2 itself has the potential to produce hyaluronan. All of these facts indicate that the spherule-like mucoid stroma and hyalinized stroma represent different phases of the stromal remodeling process, which is promoted by the deposition of different extracellular matrices produced by clear cell carcinoma cells. The spherule-like mucoid stroma and hyalinized stroma are considered complementary diagnostic signatures of ovarian clear cell carcinoma.

Vascular Lesions In Systemic Lupus Erythematosus (Sle) With Pulmonary Hypertension

An autopsy case with SLE suffering from Raynauds phenomenon and pulmonary hypertension was reported. Histological examinations revealed systemically marked fibrous intimal thickening of arteries and arterioles with or without thrombus throughout the whole body, especially of the pulmonary arteries and arterioles. Pulmonary arterial changes in the present case were compared with those in 52 autopsied cases with SLE without pulmonary hypertension, but there were no cases with such marked arterial changes as the present case. In addition, the incidence of pulmonary thrombosis was significantly higher in the cases with Raynauds phenomenon than the cases without this phenomenon. However, the relation between pulmonary hypertension and Raynauds phenomenon, pulmonary thrombosis, fibrous pericarditis, or type of lupus nephritis in SLE could not be clarified with a significant difference. ACTA PATHOL. JPN. 34: 593–604, 1984.

HISTOPATHOLOGICAL ANALYSIS OF SIXTEEN SUBCUTANEOUS RHEUMATOID NODULES

An immunopathological study was carried out on subcutaneous nodules (rheumatoid nodules) biopsied from 16 patients with rheumatoid arthritis. Sixteen rheumatoid nodules were histologically classifled into three stages; the 1st stage (acute inflammatory stage, 3 cases), the 2nd stage (granulomatous stage, 10 cases), and the 3rd stage (scar‐formed stage, 3 cases). In necrotic or granulation tissue of the nodules in the 3 stages, immunofluorescent analysis using FITC‐labeled rabbit anti‐human immunoglobulins, β1C, and flbrinogen serum γ‐globulins and FITC‐labeled aggregated human IgG gave results that were strongly positive in the 1st stage, moderately positive in the 2nd stage, and only slightly positive or almost negative in the 3rd stage. Acute or chronic thrombotic endoarteritis was observed around rheumatoid nodules in 6 out of the 16 cases. Among them, 2 cases of the 1st stage showed acute thrombotic endoarteritis with marked infiltration of neutrophils in the wall, and 2 cases of the 2nd and the 3rd stages respectively showed chronic endoarteritis with organized thrombi.

BEHÇET SYNDROME ASSOCIATED WITH NASAL MALIGNANT LYMPHOMA – REPORT OF AN AUTOPSY CASE –

The present case deals with a patient who was suffering concurrently from malignant lymphoma of the nasal cavities and Behcet disease accompanied with colitis ulcerosa.

CYSTINOSIS WITH MARKED ATROPHY OF THE KIDNEYS AND THYROID

The eldest autopsied case (a 23‐year‐old man) of infantile form of cystinosis with uremia and myxoedema was reported. The cystine content per gram wet tissue of various organs was arranged as follows: the thyroid (4.61 mg), kidney (1.71 mg), eye (0.75 mg), spleen (0.65 mg), liver (0.49 mg), and brain (0.016 mg). In polariased light microscopy, cystine crystals were detected in the epithelial cells and epithelial lumina of both kidneys by Wollaston test, and foam cells with cystine crystals were histologically found in the reticuloendothelial and other organs, especially in the bone marrows. Moreover, electron microscopic findings revealed square, rectangular or lozenge‐shaped small cystine crystal profiles in osmophilic dense bodies of the histiocytic cells and in the cytoplasm of the foam cells. In some of them, positive reaction for acid phosphatase activity was specifically localized at the periphery of the cystine crystal profiles.

Expression of a transcription factor, SOX9, in sertoli-stromal cell tumors of the ovary

Two cases of ovarian Sertoli-stromal cell tumor were examined for expression of a transcription factor, SOX9, which plays an essential role in Sertoli cell differentiation, downstream of Sry, as in the testis. By reverse transcriptase polymerase chain reaction, SOX9 mRNA was expressed in both tumors, despite the absence of Sry. These findings suggest that SOX9 expression probably plays some role in Sry-independent testicular differentiation in ovarian Sertoli-stromal cell tumors.